Stereoselective hydrolysis

Both pure L- and D-amino acids can be made using hydantoinase enzymes. These enzymes catalyze the stereoselective hydrolysis of racemic hydantoins such as (50) which is used for the production of D-alanine (15) (58). 

Esterases, proteases, and some lipases are used in stereoselective hydrolysis of esters bearing a chiral or a prochiral acyl moiety. The substrates are racemic esters and prochiral or meso-diesters. Pig liver esterase (PLE) is the most useful enzyme for this type of reaction, especially for the desymmetrization of prochiral or meso substrates. 

Enzyme-catalyzed stereoselective hydrolysis allows the preparation of enantio-merically enriched lactones. For instance. Pseudomonas sp. lipase (PSL) was found to be a suitable catalyst for the resolution of 5-undecalactone and 5-dodecalactone (Figure 6.20). Relactonization of the hydroxy acid represents an efficient method for the preparation of both enantiomers of a lactone [67]. 

Stereoselective hydrolysis of racemic l-(//-phenylacetylamino) alkanephos-phonic acids performed in the presence of penicillin acylase under the kinetic resolution conditions gave both the unreacted substrates and the products - the corresponding 1-aminophosphonic acids in high yields and with full enantioselec-tivity. The unreacted A -acyl derivatives were hydrolysed chemically and in this way each enantiomer of the free acid was obtained (Scheme 5). ... 

Finally, non-racemic phosphorothioic and phosphonothioic acids 98 were obtained via a PTE-catalysed stereoselective hydrolysis of the prochiral substrates 97 (Equation 48). ° The absolute configurations of the thioacids 98 depended on whether native PTE or its mutants were used. 

The nitrilase from cyanobacterium Synechocystis sp. PCC6803 was found to effect the stereoselective hydrolysis of phenyl-substituted /3-hydroxy nitriles to (S)-enriched /3-hydroxy carboxylic acids. The enzyme also effected the conversion of y-hydroxynitrile, albeit with lesser enantioselectivity (Table 8.10). Interestingly, this enzyme was also was found to hydrolyze aliphatic dinitriles, such that for 1,2-dicyanoethane and 1,3-dicyanopropane the... 

Huang H, Fleming CD, Nishi K, Redinbo MR, Hammock BD (2005) Stereoselective hydrolysis of pyrethroid-like fluorescent substrates by human and other mammalian liver carboxylesterases. ChemRes Toxicol 18 1371-1377... 

Stereoselective alkylations, 12 165-166 Stereoselective hydrolysis, 16 400 Stereoselective propene polymerization, catalyst symmetries for, 16 104 Stereoselectivity, in a-olefin insertion, 16 99-102... 

E. Rogalska, C. Cudrey, F. Ferrato, R. Verger, Stereoselective Hydrolysis of Triglycerides by Animal and Microbial Lipases , Chirality 1993, 5, 24-30. 

Y. I. Kageyama, Y. Yamazaki, A. S. Afify, Y. Ogawa, T. Okada, H. Okuno, Stereoselective Hydrolysis of Xenobiotic Esters by Different Cell Lines from Rat Liver and Hepatoma and Its Application to Chiral Prodrugs for Designated Growth Suppression of Cancer Cell , Chirality 1995, 7, 297 - 304. 

E. Rogalska, S. Ransac, R. Verger, Stereoselectivity of Lipases. II. Stereoselective Hydrolysis of Triglycerides by Gastric and Pancreatic Lipases , J. Biol. Chem. 1990, 265, 20271-20276. 

P. Mohr, N. Waespe-Sarcevic, C. Tamm, K. Gawronska, J. K. Gawronski, A Study of Stereoselective Hydrolysis of Symmetrical Diesters with Pig Liver Esterase , Helv. Chim. Acta 1983, 66, 2501-2511. 

R. B. Melchert, C. Goldlin, U. Zweifel, A. A. Welder, U. A. Boelsterli, Differential Toxicity of Cocaine and Its Enantiomers, (+)-Cocaine and (-)- -Cocaine, is Associated with Stereoselective Hydrolysis by Hepatic Carboxylesterases in Cultured Rat Hepatocytes , Chem.-Biol. Interact. 1992, 84, 243-258. 

K. Takahashi, J. Haginaka, S. Tamagawa, T. Nishihata, H. Yasuda, T. Katagi, Stereoselective Hydrolysis of O-Acetyl Propranolol as Prodrug in Human Serum , J. Pharm. Pharmacol. 1990, 42, 356 - 357 K. Takahashi, S. Tamagawa, J. Haginaka, H. Yasuda,... 

T. Katagi, N. Mizuno, Stereoselective Hydrolysis of O-Acetyl Propranolol as Prodrug in Rat Tissue Homogenates ,./. Pharm. Sci. 1992, 81, 226-227. 

Y. Yoshigae, T. Imai, M. Taketani, M. Otagiri, Characterization of Esterases Involved in the Stereoselective Hydrolysis of Ester-Type Prodrugs of Propranolol in Rat Liver and Plasma , Chirality 1999, 11, 10-13. 

M. Shameem, T. Imai, Y. Yoshigae, A. Sparreboom, M. Otagiri, Stereoselective Hydrolysis of O-Isovaleryl Propranolol and Its Influence on the Clearance of Propranolol after Oral Administration , J. Pharm. Sci. 1994, 83, 1754-1757. 

Y. Yoshigae, T. Imai, A. Horita, M. Otagiri, Species Differences for Stereoselective Hydrolysis of Propranolol Prodrugs in Plasma and Liver , Chirality 1997, 9, 661 -666. 

A method by Berger[12] utilized the stereoselective hydrolysis of diastereomeric peptides by leucine aminopeptidase. Z-L-Ala-D-Ala-OH was coupled to an all L-Ala peptide such as l-Ala-L-Ala-ONbz. Epimerization during coupling resulted in the formation of a small amount of L-Ala-L-Ala-L-Ala-L-Ala after deprotection, and since the peptidase has an absolute specificity for the all-L peptide, only the epimerized product was hydrolyzed. Quantification of the degradation products gave the extent of epimerization. These classical procedures, however, are specific to the particular coupling reaction under consideration and the results may not be fully applicable to all systems. Furthermore, they give no direct information about the rate of racemization. 

This unnatural acid is used as a chiral intermediate for the synthesis of a number of products. Chemical asymmetric synthesis was very difficult and so the stereoselective synthetic properties of enzymes were exploited to carry out a selective reduction reaction. The stereoselective hydrolysis of protein amino acid esters had already been commercialised by Tanabe in Japan using immobilised aminoacylase, and selective reduction reactions using whole yeast cells are already used in a number of processes, such as the selective reduction of the anti-cancer drag Coriolin. 

Whole cells are used in stirred tanks with pH control, producing fS )-2-chloropropanoic acid in 50% yield from the racemate (0.3 M) with an enantiomeric excess of over 95%. This approach was selected in preference to other methods of resolution such as acylation of the racemate and then stereoselective hydrolysis. The dehalogenase enzyme is specific for substrates with a carboxyl group and a 2-chloro or bromo substituent. No cofactor or metal ion is required and reaction involves an inversion of configuration. 

Asymmetric transformations of ot-amino acids promoted by optically active metal complexes have been reported by several groups 269). The control of the stereoselective hydrolysis reactions of racemic esters by chiral micellar compounds prepared from amino acids has been intensively investigated 270). 

The general rule based on the study of stereoselective hydrolysis of symmetrical diesters with pig liver esterase (PLE) by Tamm also predicts formation of the S enantiomer [86]. 

A study of stereoselective hydrolysis of symmetrical diesters with pig liver esterase... 

King and All butt (60, 62) have described the stereoselective hydrolysis of the dioxolenium ion 98 derived from a trans-decalin. Mild acid hydrolysis of 98 afforded almost entirely the axial ester product 99 with only a trace (<0.5%) of the equatorial ester 100. A similar result was obtained by using mild basic conditions. The authors further established by equilibration studies that the equatorial ester 100 is the most stable isomer, demonstrating that the formation of the axial isomer 99 is subject to kinetic rather than thermodynamic control. Essentially identical results were produced with two other dioxolenium salts derived from steroids. 

The complex of o-substituted anisole 203 is planar chiral, and can be used for diastereoselective generation of two new stereogenic centres in the products. Propargylation and allylation of 203 gave 204 regio- and stereoselectively. Hydrolysis of 204 afforded the cyclohexenone 205, and its intramolecular Pauson-Khand reaction gave 206 diastereoselectively. The two reactions were completely diastereoselective, and the planar chirality in 203 was efficiently transferred to the three new stereogenic centers in 206 [51]. 

Nishizawa M, Gomi H et al (1993) Purification and some properties of carboxylesterase from Arthrobacter globiformis, stereoselective hydrolysis of ethyl chrysanthemate. Biosci Biotech Biochem 57 594-598... 

Kuhn, T. Tamm, C. Riesen, A. Zehnder, M. Stereoselective hydrolysis of the dimethyl 4,5 -epoxy-1,2-cis-cyclohexanedicarboxylates with pig liver esterase. Tetrahedron Lett. 1989, 30, 693-696. 

The use of extracellular lipases of microbial origin to catalyze the stereoselective hydrolysis of esters of 3-acylthio-2-methylpropionic acid in an aqueous system has been demonstrated to produce optically active 3-acylthio-2-methyl-propionic acid [41-43], The synthesis of the chiral side chain of captopril by the lipase-catalyzed enantioselective hydrolysis of the thioester bond of racemic 3-acetylthio-2-methylpropionic acid (15) to yield 5 -(-)-(15) has been demonstrated [44], Among various lipases evaluated, lipase from Rhizopus oryzae ATCC 24563 (heat-dried cells), BMS lipase (extracellular lipase derived from the fermentation of Pseudomonas sp. SC 13856), and lipase PS-30 from Pseudomonas cepacia in an organic solvent system (l,l,2-trichloro-l,2,2-tri-fluoroethane or toluene) catalyzed the hydrolysis of thioester bond of undesired enantiomer of racemic (15) to yield desired S-(-) (15), R-(+)-3-mercapto-2-methylpropionic acid (16) and acetic acid (17) (Fig. 8A). The reaction yield of... 

The S -(-)-a-[(acetylthio)methyl]phenylpropionic acid (21) is a key chiral intermediate for the neutral endopeptidase inhibitor (22) [48], We [44] have demonstrated the lipase-catalyzed stereoselective hydrolysis of thioester bond of racemic a-[(acetylthio)methyl]phenylpropionic acid (21) in organic solvent to yield A-(+)-a-[(mercapto)methyl]phenylpropionic acid (23) and Y-(-)-(21). Using lipase PS-30, the Y-(-)-(21) was obtained in 40% reaction yield (theoretical max. 50%) and 98% e.e. (Fig. 9). 

Fig. 4 Scheme of enzymatic plasma sample preparation for enantioselective analysis of S- and fChyoscyamine. Atropine-containing plasma samples are mixed either with human serum (procedure A) or with rabbit serum (procedure B). The latter one contains atropinesterase (AtrE) whereas human serum does not. AtrE catalyses the stereoselective hydrolysis of S-Hyo, whereas f -Hyo remains unaffected. 

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